Differentially expressed microRNAs in Huh-7 cells expressing HCV core genotypes 3a or 1b: Potential functions and downstream pathways

Gu,Yu; Xu,Yuqiao; Jiang,Lina; Cao,Xiangmei; Liu,Fang; Li,Hang; Zhang,Liying; Li,Zengshan; Li,Jing; Ye,Jing; Li,Qing

doi:10.3892/ijmm.2012.991

Differentially expressed microRNAs in Huh-7 cells expressing HCV core genotypes 3a or 1b: Potential functions and downstream pathways

Authors:
- Yu Gu
- Yuqiao Xu
- Lina Jiang
- Xiangmei Cao
- Fang Liu
- Hang Li
- Liying Zhang
- Zengshan Li
- Jing Li
- Jing Ye
- Qing Li
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Affiliations: State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, P.R. China
Published online on: May 9, 2012 https://doi.org/10.3892/ijmm.2012.991
Pages: 374-382

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Abstract

microRNA (miRNA) dysfunction is believed to play important roles in human diseases, including viral infectious diseases. Hepatitis C virus (HCV) infection promotes the development of steatosis, cirrhosis and hepatocellular carcinoma, which is genotype-specific. In order to characterize the miRNA expression profile of Huh-7 cells expressing the HCV core 3a vs. 1b, microarrays and real-time PCR were performed. Consequently, 16 miRNAs (5 miRNAs upregulated and 11 miRNAs downregulated) were found to be dysregulated. In addition, we generated the predicted and validated targets of the differentially expressed miRNAs and explored potential downstream function categories and pathways of target genes using databases of Gene Ontology (GO) and PANTHER and the database for annotation, visualization and integrated discovery (David). The computational results indicated that the dysregulated miRNAs might perform the functions of cellular metabolism and cellular growth. Finally, these biological effects were preliminarily validated. This study identifies a specific miRNA expression profile in cells expressing HCV core proteins of different genotypes (genotype 3a and 1b), which may account for the variable pathophysiological manifestation associated with HCV infection.

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1.	S KhaliqS JahanA PervaizSequence variability of HCV core region: important predictors of HCV induced pathogenesis and viral productionInfect Genet Evol11543556201110.1016/j.meegid.2011.01.01721292033
2.	M ArreseA RiquelmeA SozaInsulin resistance, hepatic steatosis and hepatitis C: a complex relationship with relevant clinical implicationsAnn HepatolSuppl 9S112S118201020714007
3.	M RipoliV PazienzaImpact of HCV genetic differences on pathobiology of diseaseExpert Rev Anti Infect Ther9747759201110.1586/eri.11.9421905784
4.	V PazienzaS ClementP PugnaleGene expression profile of Huh-7 cells expressing hepatitis C virus genotype 1b or 3a core proteinsLiver Int29661669200910.1111/j.1478-3231.2008.01866.x18803589
5.	L WuJG BelascoLet me count the ways: mechanisms of gene regulation by miRNAs and siRNAsMol Cell2917200810.1016/j.molcel.2007.12.01018206964
6.	X PengY LiKA WaltersComputational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human liversBMC Genomics10373200910.1186/1471-2164-10-37319671175
7.	NM SteuerwaldJC ParsonsK BennettTC BatesHL BonkovskyParallel microRNA and mRNA expression profiling of (genotype 1b) human hepatoma cells expressing hepatitis C virusLiver Int3014901504201010.1111/j.1478-3231.2010.02321.x
8.	CL JoplingM YiAM LancasterSM LemonP SarnowModulation of hepatitis C virus RNA abundance by a liver-specific microRNAScience30915771581200510.1126/science.111332916141076
9.	K AbidV PazienzaA de GottardiAn in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulationJ Hepatol42744751200510.1016/j.jhep.2004.12.03415826725
10.	X JinYP ChenM KongL ZhengYD YangYM LiTransition from hepatic steatosis to steatohepatitis: unique microRNA patterns and potential downstream functions and pathwaysJ Gastroenterol Hepatol27331340201110.1111/j.1440-1746.2011.06864.x21793903
11.	W Huang daBT ShermanQ TanDAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene listsNucleic Acids Res35W169W175200717576678
12.	J FolchM LeesGH Sloane StanleyA simple method for the isolation and purification of total lipides from animal tissuesJ Biol Chem226497509195713428781
13.	JH HoofnagleHepatitis C: the clinical spectrum of diseaseHepatology26Suppl 1S15S20199710.1002/hep.510260703
14.	OM KlibanovSH WilliamsLS SmithJL OlinSB VickeryTelaprevir: a novel NS3/4 protease inhibitor for the treatment of hepatitis CPharmacotherapy31951974201110.1592/phco.31.10.95121950642
15.	C JoplingLiver-specific microRNA-122: Biogenesis and functionRNA Biol9137142201210.4161/rna.1882722258222
16.	IM PedersenG ChengS WielandInterferon modulation of cellular microRNAs as an antiviral mechanismNature449919922200710.1038/nature0620517943132
17.	MW FriedM ShiffmanRK SterlingA multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis c: pretreatment stratification by viral burden and genotypeAm J Gastroenterol9532253229200010.1111/j.1572-0241.2000.03433.x11095346
18.	S ChevaliezT AsselahMechanisms of non-response to antiviral treatment in chronic hepatitis CClin Res Hepatol Gastroenterol35Suppl 1S31S41201110.1016/S2210-7401(11)70005-521742299
19.	C CammaS BrunoV Di MarcoInsulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis CHepatology436471200610.1002/hep.2098316374856
20.	S BrunoA CrosignaniP MaisonneuveS RossiE SiliniMU MondelliHepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort studyHepatology4613501356200717680653
21.	J LinS HuangS WuMicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting p21Cip1/Waf1 in hepatocellular carcinomaCarcinogenesis3216411647201110.1093/carcin/bgr19921890460
22.	S SenguptaJ NieRJ WagnerC YangR StewartJA ThomsonMicroRNA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cellsStem Cells2715241528200910.1002/stem.8419544458
23.	C YiQ WangL WangmiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinomaOncogeneJan162012(Epub ahead of print)
24.	S YoonYC ChoiS LeeY JeongJ YoonK BaekInduction of growth arrest by miR-542-3p that targets survivinFEBS Lett58440484052201010.1016/j.febslet.2010.08.02520728447
25.	EA AfanasyevaP MestdaghC KumpsMicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survivalCell Death Differ18974984201110.1038/cdd.2010.16421233845
26.	S FengS CongX ZhangMicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cellsNucleic Acids Res3966696678201110.1093/nar/gkr23221511813
27.	Y WangCG LeeRole of miR-224 in hepatocellular carcinoma: a tool for possible therapeutic intervention?Epigenomics3235243201110.2217/epi.11.522122284
28.	YM LeeJY LeeCC HoMicroRNA 34b as a tumor suppressor in estrogen-dependent growth of breast cancer cellsBreast Cancer Res13R116201110.1186/bcr305922113133
29.	Z HuangS HuangQ WangMicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinomaCancer Res7125822589201110.1158/0008-5472.CAN-10-303221427358
30.	LE ZaragosiB WdziekonskiKL BrigandSmall RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesisGenome Biol12R64201110.1186/gb-2011-12-7-r6421767385
31.	LP LimNC LauP Garrett-EngeleMicroarray analysis shows that some microRNAs downregulate large numbers of target mRNAsNature433769773200510.1038/nature0331515685193
32.	A PiodiP ChouteauH LeratC HezodeJM PawlotskyMorphological changes in intracellular lipid droplets induced by different hepatitis C virus genotype core sequences and relationship with steatosisHepatology481627200810.1002/hep.22288
33.	C Jackel-CramLA BabiukQ LiuUp-regulation of fatty acid synthase promoter by hepatitis C virus core protein: genotype-3a core has a stronger effect than genotype-1b coreJ Hepatol469991008200710.1016/j.jhep.2006.10.01917188392
34.	E SoupeneFA KuypersMammalian long-chain acyl-CoA synthetasesExp Biol Med (Maywood)233507521200810.3181/0710-MR-28718375835
35.	JS BurgPJ EspenshadeRegulation of HMG-CoA reductase in mammals and yeastProg Lipid Res50403410201110.1016/j.plipres.2011.07.00221801748
36.	I OnoyamaA SuzukiA MatsumotoFbxw7 regulates lipid metabolism and cell fate decisions in the mouse liverJ Clin Invest121342354201010.1172/JCI4072521123947
37.	CJ LoewenTP LevineCholesterol homeostasis: not until the SCAP lady INSIGsCurr Biol12R779R781200210.1016/S0960-9822(02)01292-712445404
38.	S MartinRG PartonCaveolin, cholesterol, and lipid bodiesSemin Cell Dev Biol16163174200510.1016/j.semcdb.2005.01.00715797827
39.	K KlappeI HummelD HoekstraJW KokLipid dependence of ABC transporter localization and functionChem Phys Lipids1615764200910.1016/j.chemphyslip.2009.07.00419651114
40.	LB AgellonL DrozdowskiL LiLoss of intestinal fatty acid binding protein increases the susceptibility of male mice to high fat diet-induced fatty liverBiochim Biophys Acta177112831288200710.1016/j.bbalip.2007.08.00417905650
41.	E SchmittMA BallouMN CorreaEJ DePetersJK DrackleyJJ LoorDietary lipid during the transition period to manipulate subcutaneous adipose tissue peroxisome proliferator-activated receptor-gamma co-regulator and target gene expressionJ Dairy Sci9459135925201110.3168/jds.2011-4230
42.	Y ColakO OzturkE SenatesSIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver diseaseMed Sci Monit17HY59201110.12659/MSM.88174921525818
43.	E GlasgowL MishraTransforming growth factor-beta signaling and ubiquitinators in cancerEndocr Relat Cancer155972200810.1677/ERC-07-016818310276
44.	SS ThorgeirssonT TeramotoVM FactorDysregulation of apoptosis in hepatocellular carcinomaSemin Liver Dis18115122199810.1055/s-2007-10071489606809
45.	K BreuhahnP SchirmacherReactivation of the insulin-like growth factor-II signaling pathway in human hepatocellular carcinomaWorld J Gastroenterol1416901698200810.3748/wjg.14.169018350600
46.	S JahanUA AshfaqS KhaliqB SamreenN AfzalDual behavior of HCV core gene in regulation of apoptosis is important in progression of HCCInfect Genet Evol12236239201210.1016/j.meegid.2012.01.00622266242